Efficient Synthesis of (±)-Dihydrorhipocephalin,a Bioactive Terpenoid from Caribbean Marine Algae of the Genera Penicillus and Udotea

Laurent Commeiras; Robert Valls; Maurice Santelli; Jean-Luc Parrain

doi:10.1055/s-2003-41008

LETTER

Efficient Synthesis of (±)-Dihydrorhipocephalin,a Bioactive Terpenoid from Caribbean Marine Algae of the Genera Penicillus and Udotea

Laurent Commeiras^a, Robert Valls^b, Maurice Santelli^a, Jean-Luc Parrain*^a
^a Laboratoire de Synthèse au Organiqueassocié CNRS (UMR 6009), Faculté desSciences de Saint Jérôme, AvenueEscadrille Normandie-Niemen, 13397 Marseille Cedex 20,France
e-Mail: jl.parrain@univ.u-3mrs.fr;
^b Laboratoire des Organophosphorés associé auCNRS (UMR 6009), Faculté des Sciencesde Saint Jérôme, Avenue Escadrille Normandie-Niemen,13397 Marseille Cedex 20, France

Abstract

All articles of this category

Abstract

The first total synthesis of (±)-dihydrorhipocephalin fromCaribbean marine algae of the genera Penicillus and Udotea was accomplished, in few steps,controlling the construction of 2-substituted 1,4-diacetoxybutadienemoiety and the configuration of the central double bond.

Key words

(±)-dihydrorhipocephalin - bioactive terpenoid - total synthesis

Full Text

References

1 Paul VJ. Fenical W. Tetrahedron 1984, 40: 2913

2a Paul VJ. Fenical W. MarineEcology-Progress Series 1986, 34: 157

2b Mayer AMS. Paul VJ. Fenical W. Norris JN. de Carvalho MS. Jacobs RS. Hydrobiologia 1993, 260: 521

2c Mayer AMS. Paul VJ. Fenical W. Norris JN. de Carvalho MS. Jacobs RS. Hydrobiologia 1993, 261: 521

3 Commeiras L. Santelli M. Parrain JL. Org.Lett. 2001, 3: 1713

4 Kocienski P. Wadman S. Cooper K. J.Org. Chem. 1989, 54: 1215

5 Wenkert E. Michelotti EL. Swindell CS. Tingoli M. J. Org Chem. 1984, 49: 4894

6 Dess DB. Martin JC. J. Am. Chem. Soc. 1991, 113: 7277

7 Zhang HX. Guibé F. Balavoine G. J.Org. Chem. 1990, 55: 1857

8a Barrett AGM. Barta TE. Flygare JA. J.Org. Chem. 1989, 54: 4246

8b Steinig AG. de Meijere A. Eur.J. Org. Chem. 1999, 1333

9 Nicolaou KC. Seitz SP. Pavia MR. Petasis NA. J. Org. Chem. 1979, 44: 4011

10 Commeiras L. Santelli M. Parrain JL. TetrahedronLett. 2003, 44: 2311

11

In Schlenk tube, under nitrogen atmosphere,were placed 23 mg (0.068 mmol) of 10, 8.3mg (0.068 mmol) of DMAP, 19 µL (0.2 mmol) of Ac₂Oand 1.5 mL of Et₃N. The mixture was then warmed to 80 °Cand the reaction was followed by GC. After disappearance of thestarting material, the mixture was concentrated in vacuo and purifiedby chromatography on silica gel (pentane/EtOAc: 8/2)to give a 45/55 mixture of dihydrorhipocephalin 1 and iso-dihydrorhipocephalin(1′) (80% yield). Dihydrorhipocephalin(1): ¹H NMR (500 MHz, CDCl₃): δ = 1.57(s, 3 H,), 1.59 (s, 3 H), 1.65 (s, 3 H), 1.93-2.05 (m,4 H), 2.03 (s, 3 H), 2.13 (s, 3 H), 2.16 (s, 3 H), 2.37 (dt, J = 14.3,7.3 Hz, 1 H), 2.52 (dt, J = 14.3, 7.3 Hz, 1 H), 5.02-5.05(m, 4 H), 5.80 (d, J = 12.7Hz, 1 H), 5.83 (t, J = 7.3Hz, 1 H), 7.20 (s, 1 H), 7.61 (d, J = 12.7Hz, 1 H). iso-Dihydrorhipocephalin (1′): ¹H NMR(500 MHz, CDCl₃): δ = 1.57 (s, 3 H,),1.59 (s, 3 H), 1.65 (s, 3 H), 1.93-2.05 (m, 4 H), 2.01(s, 3 H) 2.18 (m, 6 H), 2.26 (dt, J = 14.3, 7.3 Hz, 1 H), 2.44(dt, J = 14.3,7.3 Hz), 5.02-5.05 (m, 4 H), 5.20 (d, J = 7.3Hz, 1 H), 5.85 (t, J = 7.3 Hz, 1 H), 7.21(d, J = 7.3 Hz,1 H), 7.80 (s, 1 H). ¹³C NMR of compound 1 and 1′ (125 MHz,CDCl₃): δ = 16.30, 16.40, 17.70 (2C), 20.80 (2 C), 20.85, 20.88, 21.10, 21.20, 25.70 (2 C), 26.70(2 C), 31.60, 31.90, 39.79, 39.82, 69.40, 69.50, 104.00, 109.50,117.30, 118.06, 118.11, 119.20, 124.00 (2 C), 131.60, 131.61, 134.00,134.90, 137.00, 137.50, 138.80, 138.90, 167.20, 167.30, 167.50,167.90, 170.10 (2 C).

12

HPLC separation was done using a (S,S)-Whelk-O1 column with 5 micron packing (25 cm × 4.6 mm using a95:5 mixture of hexane and 2-PrOH).